Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry最新文献

Background: Burns induce a boost in local and systemic complement levels as well as immune cell infiltration in the burn wound, which may negatively affect wound healing.

Objective: In this study, the effects of long-term treatment with complement inhibitor C1 esterase inhibitor (C1inh) on post-burn inflammation and wound healing parameters were analyzed in time up to 60 days post-burn.

Methods: Burned pigs were treated either with or without C1inh up to 15 days post-burn. Burn wound biopsies and blood were collected at different time points up to 60 days post-burn. Thereafter, complement in blood as well as complement and immune cells in the wound, capillary leakage, necrosis, reepithelialization and wound contraction were quantified.

Results: No significant differences in complement C3 blood levels were observed at any time point between C1inh-treated and control pigs. In the wound, complement C4 levels were significantly lower in the C1inh group than in controls at day 3-6 and 21-30 post-burn. Similarly, C3 levels, neutrophil and macrophage infiltration in the wound were, although not statistically significant, reduced in C1inh-treated pigs at day 9-14 post-burn. No differences in lymphocyte infiltration in the wound were found between C1inh and control pigs. C1inh-treated pigs also showed reduced capillary leakage. Despite these effects, no significant differences in the long-term wound healing parameters necrosis, reepithelialization and wound contraction were observed between C1inh and control pigs.

Conclusion: In pigs, 15 days of C1inh treatment after burn, leads to a reduction in local inflammation and capillary leakage in the burn wound without affecting long-term wound healing parameters.

Background: 3,4,5-Trihydroxybenzoic acid, which is also known as gallic acid, is an antiinflammatory agent that could provide beneficial effects in preventing periodontal inflammation. The present study aimed to evaluate the anti-inflammatory effects of gallic acid on experimental periodontitis in Wistar rats. Alveolar bone loss, osteoclastic activity, osteoblastic activity, and collagenase activity were also determined.

Methods: Thirty-two Wistar rats were used in the present study. Study groups were created as following: Healthy control (C,n=8) group; periodontitis (P,n=8) group; periodontitis and 30 mg/kg gallic acid administered group (G30,n=8); periodontitis and 60 mg/kg gallic acid administered group (G60,n=8). Experimental periodontitis was created by placing 4-0 silk sutures around the mandibular right first molar tooth. Morphological changes in alveolar bone were determined by stereomicroscopic evaluation. Mandibles were undergone histological evaluation. Matrix metalloproteinase (MMP)-8, tissue inhibitor of MMPs (TIMP)-1, bone morphogenetic protein (BMP)-2 expressions, tartrateresistant acid phosphatase (TRAP) positive osteoclast cells, osteoblast, and inflammatory cell counts were determined.

Results: The highest alveolar bone loss was observed in the periodontitis group. Both doses of gallic acid decreased alveolar bone loss as compared to the P group. TRAP-positive osteoclast cell counts were higher in the P group, and gallic acid successfully lowered these counts. Osteoblast cells also increased in gallic acid administered groups. Inflammation in the P group was also higher than those of C, G30, and G60 groups supporting the role of gallic acid in preventing inflammation. 30 and 60 mg/kg doses of gallic acid decreased MMP-8 levels and increased TIMP-1 levels. BMP levels increased in gallic acid administered groups, similar to several osteoblasts.

Conclusion: Present results revealed an anti-inflammatory effect of gallic acid, which was indicated by decreased alveolar bone loss and collagenase activity and increased osteoblastic activity.

Background: Antibiotics used parenterally can affect blood drug level measurements, as measured in diagnostic tests.

Objective: To investigate the effect of six different antibiotics commonly used in intensive care units on tacrolimus, sirolimus, everolimus and cyclosporin A levels measured by mass spectrometry.

Methods: Ampicillin + sulbactam (AB1, IV, 1 g), imipenem + cilastatin sodium (AB2, IV, 500 mg), piperacillin + tazobactam (AB3, 4.5 g, IV), ertapenem (AB4, IV, 1 g), meropenem trihydrate (AB5, 500 mg, IV) and ceftriaxone (AB6, 1 g, IV) antibiotics were used for the interference assay. Measurements were performed on the Shimadzu 8045 (Japan) LC-MS/MS instrument. Bias values were calculated.

Results: The least affected immunosuppressant was cyclosporine A (between -6.88% and 3.40%). The most affected were everolimus and sirolimus. Ertapenem caused negative interference on the level of everolimus at the rate of -27.34% and sirolimus at the rate of -26.79%. Piperacillin + tazobactam and imipenem + cilastatin sodium caused positive interferences on sirolimus at the rate of 24.24% and 22.73%, respectively. Ampicillin + sulbactam, meropenem trihydrate and ceftriaxone affected the sirolimus levels at lower rates (-4.49%, 5.93% and 9.86%). Everolimus levels deviated at the rate of -11.21% to -16.99% due to imipenem + cilastatin sodium, meropenem trihydrate and ceftriaxone.

Conclusion: This study demonstrated the potential of antibiotic use affecting immunosuppressant levels. Antibiotic interference, especially in transplant patients, may cause erroneous immunosuppression, increasing the likelihood of rejection.

Introduction: Newborn screening (NBS) by quantifying T cell receptor excision circles (TRECs) and Kappa receptor excision circles in neonatal dried blood spots (DBS) enables early diagnosis of different types of primary immune deficiencies. Global newborn screening for PID, using an assay to detect T-cell receptor excision circles (TREC) in dried blood spots (DBS), is now being performed in all states in the United States. In this review, we discuss the development and outcomes of TREC, TREC/KREC combines screening, and continued challenges to implementation.

Objective: To review the diagnostic performance of published articles for TREC and TREC/ KREC based NBS for PID and its different types.

Methods: Different research resources were used to get an approach for the published data of TREС and KREC based NBS for PID like PubMed, Scopus, Google Scholar, Research gate EMBASE. We extracted TREC and KREC screening Publisher with years of publication, content and cut-off values, and a number of retests, repeat DBS, and referrals from the different published pilot, pilot cohort, Case series, and cohort studies.

Results: We included the results of TREC, combined TREC/KREC system based NBS screening from different research articles, and divided these results between the Pilot studies, case series, and cohort. For each of these studies, different parameter data are excluded from different articles. Thirteen studies were included, re-confirming 89 known SCID cases in case series and reporting 53 new SCID cases in 3.15 million newborns. Individual TREC contents in all SCID patients were <25 TRECs/μl (except in those evaluated with the New York State assay).

Conclusion: TREC and KREC sensitivity for typical SCID and other types of PID was 100 %. It shows its importance and anticipating the significance of implementation in different undeveloped and developed countries in the NBS program in upcoming years. Data adapting the screening algorithm for pre-term/ill infants reduce the amount of false-positive test results.

Background & aims: Pruritus associated with liver diseases confines daily activities and causes sleep deprivation in patients with chronic liver diseases. Autotoxin enzyme (ATX) was found to be higher in sera of patients with intrahepatic cholestasis and it was found to be associated with the intensity of itching. The aim of this study was to assess the correlation between the autotaxin enzyme and pruritus in Egyptian patients suffering from chronic liver disease (CLD).

Methods: This cross-sectional study was carried on a total number of 80 patients with chronic liver disease divided into four groups: Group A and B included cirrhotic patients suffering from pruritis with and without cholestasis, while group C and D included patients without pruritis with or without cholestasis and group E included 17 healthy controls. They were subjected to measurement of serum autotoxin concentration by ELISA in addition to routine investigations including liver function tests: Total and direct bilirubin, ALT, AST, Alkaline phosphatase, Gama- glutamyl transferase, and serum albumin.

Results: There was a significant increase in autotaxin in the four groups included chronic liver disease patients (P-value <0.001*) compared to control group (group E). Autotoxin level was the only marker that had a significant increase in pruritus groups (groups A & B) compared to non-pruritus groups (groups C & D) with cut off value ≥ 32.

Conclusion: Serum autotaxin level was elevated in patients with chronic liver diseases with pruritus. Autotaxin enzyme may play a key role in the induction of hepatogenic pruritus. So, autotaxin enzyme inhibitors and lysophosphatidic acid (LPA) receptor blockers could be a future line of treatment of hepatogenic pruritus.

Pediatric atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease, affecting 20% of children all over the world especially in developed countries. The global prevalence of AD in children has been increasing over recent years. This chronic inflammatory skin disease causes economic and social burden to the family. The exact cause of AD is not known, however recent studies suggest that the imbalance of microflora present in the gut leads to AD. The current treatment of AD involves the application of moisturizer, topical corticosteroids, antihistamines and antibiotics. This line of treatment of AD in children has many side effects. An alternative novel therapeutic approach has to be explored to combat this chronic skin disease. In recent years, there has been increasing interest in the use of probiotics in the modulation of gut microbiota for the management of AD. Many research studies showed that the administration of probiotics gives positive results in the prevention and treatment of AD in children, however, the results are not consistent and conclusive. In this review, the phenomenon that the dysbiosis of the gut flora contributes to the development of AD is addressed and clinical evidence of probiotics in the prevention and treatment of AD children is also summarised.

Background: In the Iraqi community, abnormal pregnancy forms a major social and psychological health problem. The underlying etiology of this health phenomenon was varied and included sets of infections and autoimmune diseases. Globally human parvovirus 19 infection is common and the infection attributes to bad obstetric outcomes. The global maternal parvovirus B19 remote infection rate was within a range of 13.2% to 97.9%, while the range of acute infection was between 0.5% to 97.9%. In Arab countries, the IgG seroprevalence was from 53.3% to 74%, while IgM seroprevalence range was 2.2% to 84%.

Objective: To evaluate the role of ParvovirusB19 as an etiology of bad obstetric outcome in women in Kirkuk, Iraq.

Materials and methods: Descriptive Case Control Study. Women included in the study were recruited from Kirkuk General Hospital and their age ranged from 14 to 48 years. A total of 663 women were included in the study, of them 237 were not pregnant, while 215 were pregnant. Additionally, the study included 211 women with inevitable abortion. Control group (306 women) women with a history of normal pregnancy included (Pregnant= 149; non-pregnant= 157). Clinical and laboratory investigations were conducted on all patients and control groups to exclude other causes. Medical and obstetric data and demographic characteristics were gathered through interviews according to a previously designed questionnaire. ELISA kits were used to determine Parvovirus B19 IgM and IgG antibodies.

Results: The overall parvovirus seroprevalence was 93% and with no significant difference between women with normal (89.5%) and those with abnormal (93.1%) pregnancy outcomes. In addition, parvovirus IgM overall seroprevalence was at56.3%. Furthermore, current parvovirus infection was higher in women with BOH (52.6%) than that in women with normal pregnancy (49.7%) outcomes. Parvovirus IgM seroprevalence was 52.6% in women with BOH and 49.7% in women with normal pregnancy, however, the difference was not statistically significant. In contrast, the acute infection with parvovirus was significantly (X2=11.8, P=0.001) lower in women with normal pregnancy (49.7%) than in those with inevitable abortion (64.9%). While the IgG seroprevalence difference was not significant between the two groups, infection seroprevalence was more frequent in housewives, uneducated women, large families, non-smokers, in rural areas, non-animal exposure areas, women with repeated abortion, congenital anomalies and anaemia.

Conclusion: Parvovirus B19 infection may be with bad obstetric outcomes if occurred during pregnancy and OR confirmed a significant association of the infection with parvovirus with smoking, occupation, crowding index, education, animal exposure and the number of repeated abortion.

Aims & background: The early diagnosis of spontaneous bacterial peritonitis (SBP) has been considered important in the overall patient's survival. Ascitic fluid culture examination performance, in the emergency setting, is time-consuming and not always available, so there is a need for easy to apply, rapid and reliable markers for diagnosis of patients with ascites. The present prospective study aimed to determine the early diagnostic value of serum procalcitonin (PCT) levels in decompensated cirrhotic patients (DCPs) with SBP.

Methods: 47 HCV cirrhotic patients with ascites were enrolled for this prospective study. The severity of cirrhosis was classified based on the Child-Pugh criteria. All patients were subjected to paracentesis and ascitic fluid (AF) culture. Serum PCT levels were measured using enzyme-linked fluorescence analysis (ELFA).

Results: The diagnostic value of serum PCT levels and WBC/PLT ratios for detecting infections were serum PCT levels (3.63 ± 3.47 ng/mL) in DCPs with infections which were significantly higher than in DCPs without infections (0.505 ± 0.230 ng/mL); p < 0.05. The cut-off value for serum PCT levels was 0.7 ng/mL for the diagnosis of infections in DCPs, for which the sensitivity and specificity were 93.1% and 73.2%, respectively. The AUC was 0.91 (95% CI: 0.83-0.99).

Conclusion: Serum procalcitonin seems to provide satisfactory diagnostic biomarkers in SBP.

Background: Antivenom is a gold-standard treatment for snakebite envenoming. However, adverse reactions to snake antivenom are common in many parts.

Objective: The aim of this study was to evaluate the allergic reactions following intravenous administration of antivenom sera.

Methods: This was retrospective study conducted on snakebites patients referred to the Rahimi Hospital in Khorramabad. The files of these patients were accessed for demographic data, snakebite-related data, treatment provided, clinical presentation and allergic reaction status as a result of antivenom treatment.

Results: 141 cases were investigated, including 73.8% male and 26.2% female patients. The mean age of the patients was 38.1±17.1 years. Age group 30-39 years accounted for the highest number of snakebite cases (24.1%). A majority of victims (89.4%) were from rural areas. Most of the patients (51.8%) were bitten in the spring and highest number of snakebite were reported in May (39.1%). The most common site of snakebite was lower extremities (50.4%) and upper extremities (44.7%). Among clinical feature of snakebite, pain was the most prevalent in 135 cases (95.7%) followed by swelling (83.7%). The mean antivenom vials used were 6.5±3.7 vials. Allergic reactions occurred in 6 patients (4.26%); reactions were mild in 5 patients and severe in 1 patient. The commonest presentation was maculopapular rash (1.4%) and the least common were headache (0.71%), nausea (0.71%), fever (0.71) and hypotension (0.71%).

Conclusion: Snakebite is one of the significant life-threatening environmental events. Immediate antivenom treatment can reduce mortality however, patients should be carefully monitored for adverse allergic reactions.

Background: Spontaneous bacterial peritonitis is a common bacterial infection of ascitic fluid, mainly in ascites due to liver cirrhosis. Mannose-binding lectin (MBL) can activate phagocytosis and the complement system. Spontaneous bacterial peritonitis was detected to be higher in MBL deficiency. This study aimed to assess ascitic fluid MBL in liver cirrhosis and spontaneous bacterial peritonitis.

Methods: Ninety patients with cirrhotic ascites were included. Forty five of them had SBP. Child- Pugh score, Model for End Stage Liver Disease (MELD) and its update (uMELD) scores were used to assess the severity of liver cirrhosis. Ascitic fluid samples were obtained for differentiation of leucocytic count, estimation of albumin, protein, glucose, and serum-ascitic albumin gradient. Ascitic fluid levels of MBL were measured for all patients. SBP was documented if polymorphonuclear leucocytic count ≥250/mm in ascitic fluid.

Results: Ascitic fluid MBL level was significantly lower in patients with SBP. MBL had a significant negative correlation with ascitic total leukocytic count (TLC), also with serum creatinine, bilirubin, PT, INR and MELD score among SBP patients. However, it had a significant positive correlation with ascitic protein and with platelets. According to multivariate analysis, fever, TLC, platelets, creatinine, MBL, glucose and polymorphs were independent predictors for SBP development.

Conclusion: Ascitic fluid MBL could be a good predictive and prognostic marker in patients with cirrhosis and spontaneous bacterial peritonitis.